rs1057516055
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
Variant has been reported in ClinVar as Uncertain significance (★★★).
Frequency
Mitomap GenBank:
𝑓 0.0 ( AC: 1 )
Consequence
TRNV
stop_lost
stop_lost
Scores
Mitotip
Uncertain
Clinical Significance
Charcot-Marie-Tooth-(CMT)
Conservation
PhyloP100: 0.0530
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very low frequency in mitomap database: 0.0
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| TRNV | unassigned_transcript_4787 use as main transcript | c.60A>G | p.Ter20Trpext*? | stop_lost | 1/1 | |||
| RNR2 | unassigned_transcript_4788 use as main transcript | n.-10A>G | upstream_gene_variant | |||||
| use as main transcript |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|
Frequencies
GnomAD4 exome Cov.: 0
GnomAD4 exome
Cov.:
0
We have no GnomAD4 genomes data on this position. Probably position not covered by the project.
Mitomap GenBank
AF:
AC:
1
Gnomad homoplasmic
AF:
AC:
2
AN:
56398
Gnomad heteroplasmic
AF:
AC:
3
AN:
56398
Mitomap
Charcot-Marie-Tooth-(CMT)
ClinVar
Significance: Uncertain significance
Submissions summary: Pathogenic:2Uncertain:3
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
Charcot-Marie-Tooth disease, axonal, mitochondrial form, 1 Pathogenic:1
| Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 17, 2024 | - - |
SPASTIC PARAPLEGIA, MITOCHONDRIAL Pathogenic:1
| Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 17, 2024 | - - |
not specified Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Mendelics | May 04, 2022 | - - |
Mitochondrial disease Uncertain:1
| Uncertain significance, reviewed by expert panel | curation | ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel, ClinGen | Oct 23, 2023 | The m.1661A>G variant in MT-TV has been reported in two unrelated families (PS4_supporting). Limited phenotypic details are provided in the first reported family (Patient 6 in Bacalhau et al., 2017, PMID: 28027978) however a subsequent publication reported the proband in this family had seizures, hypotonia, developmental delay, elevated blood lactate, and combined deficiency of electron transport chain enzyme activities (PMID: 32715519). The heteroplasmy level and information on family members and/or testing in family members were not reported in this first kindred. The second family reported was a large kindred from the Venezuelan Andes with axonal Charcot-Marie-Tooth (CMT) disease (motor and sensory neuropathy). Muscle weakness, muscle atrophy, and ataxia were also seen in the affected individuals in this family (Fay et al., 2020, PMID: 32715519). Muscle biopsies performed in several individuals showed denervation and reinnervation, in addition to mitochondrial hyperplasia, mildly increased glycogen, and the presence of mitochondrial crystalline arrays. Combined respiratory chain enzyme deficiencies were also seen in affected individuals from this kindred. The variant was present at homoplasmy in blood and/or muscle in both affected and unaffected individuals from this kindred. There are no reported de novo occurrences on this variant to our knowledge. The computational predictor MitoTIP suggests this variant is benign (27.6 percentile; BP4).This variant is present in population databases (MITOMAP: 1/61,168 sequences, AF=0.002%, haplogroup (Hg) H1c; Helix: 2/195,983 (0.001%), also 19 heteroplasmic occurrences, homoplasmic occurrences in Hg I and V, heteroplasmic in multiple haplogroups; and gnomAD v3.1.2: 2/56,398 (0.004%), also three heteroplasmic occurrences (heteroplasmy levels: 10-20%; 20-30%; 90-100%), one in Hg T, one in H, one in B, one in K, one in L3). Given the frequency of this variant, it does not meet PM2 criterion. There are no cybrids, single fiber studies, or other functional assays reported on this variant. In summary, this variant meets criteria to be classified as uncertain significance for primary mitochondrial disease inherited in a mitochondrial manner. This classification was approved by the NICHD/NINDS U24 ClinGen Mitochondrial Disease Variant Curation Expert Panel on October 23, 2023. Mitochondrial DNA-specific ACMG/AMP criteria applied (PMID: 32906214): PS4_supporting, BP4 - |
Epilepsy;C0424605:Developmental delay;C1853743:Axial hypotonia;CN239816:Hyperlactaemia Uncertain:1
| Uncertain significance, no assertion criteria provided | clinical testing | Center for Neuroscience and Cell Biology, University of Coimbra, Portugal | Nov 21, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Mitotip
Uncertain
Hmtvar
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at